Multiple Sclerosis Journal - October 2017 - 1469

681504
research-article2016

MSJ0010.1177/1352458516681504Multiple Sclerosis JournalG Datta, IR Violante

MULTIPLE
SCLEROSIS
JOURNAL

MSJ

Original Research Paper

Translocator positron-emission tomography
and magnetic resonance spectroscopic imaging
of brain glial cell activation in multiple
sclerosis

Multiple Sclerosis Journal
2017, Vol. 23(11) 1469-1478
DOI: 10.1177/
https://doi.org/10.1177/1352458516681504
1352458516681504
https://doi.org/10.1177/1352458516681504
© The Author(s), 2016.
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Gourab Datta, Ines R Violante, Gregory Scott, Karl Zimmerman, Andre Santos-Ribeiro,
Eugenii A Rabiner, Roger N Gunn, Omar Malik, Olga Ciccarelli, Richard Nicholas
and Paul M Matthews

Abstract
Background: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by
microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and
[myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this.
Objective: To explore the in vivo relationships between MRS and PET [11C]PBR28 in MS over a range
of brain inflammatory burden.
Methods: A total of 23 patients were studied. TSPO PET imaging with [11C]PBR28, single voxel MRS
and conventional magnetic resonance imaging (MRI) sequences were undertaken. Disability was assessed
by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC).
Results: [11C]PBR28 uptake and [myo-inositol] were not associated. When the whole cohort was stratified by higher [11C]PBR28 inflammatory burden, [myo-inositol] was positively correlated to [11C]PBR28
uptake (Spearman's ρ = 0.685, p = 0.014). Moderate correlations were found between [11C]PBR28 uptake
and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume.
MSFC was correlated with grey matter volume (ρ = 0.535, p = 0.009). There were no associations between
other imaging or clinical measures.
Conclusion: MRS [myo-inositol] and PET [11C]PBR28 measure independent inflammatory processes
which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [11C]PBR28 uptake was associated with loss of neuronal integrity and grey matter
atrophy.
Keywords: Multiple sclerosis, glia, biomarkers, MRI
Date received: 11 September 2016; revised: 19 October 2016; accepted: 26 October 2016
Introduction
Multiple sclerosis (MS) is a chronic inflammatory
condition characterised by focal and diffuse demyelination and neurodegeneration in the central nervous
system (CNS). The brain's chronic inflammatory
response includes astrocyte activation and microglial
activation, as well as recruitment of peripheral macrophages. This chronic inflammation is associated
with neurodegeneration and disability progression.1,2
Conventional magnetic resonance imaging (MRI)
detects acute white matter inflammatory lesions and

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consequent demyelination and gliosis. However,
it lacks sensitivity and specificity for quantifying
chronic inflammation and the associated neuronal
injury.

Correspondence to:
PM Matthews
E515, Division of Brain
Sciences, Department of
Medicine, Imperial College
London, The Hammersmith
Hospital, DuCane Road,
London WC12 0NN, UK.
p.matthews@imperial.ac.uk
Gourab Datta
Ines R Violante
Gregory Scott
Karl Zimmerman
Andre Santos-Ribeiro
Omar Malik
Richard Nicholas
Paul M Matthews
Division of Brain Sciences,
Department of Medicine,
Imperial College London,
London, UK
Eugenii A Rabiner
Imanova Ltd, Imperial
College London, London,
UK/Centre for Neuroimaging
Sciences, King's College
London, London, UK
Roger N Gunn
Division of Brain Sciences,
Department of Medicine,
Imperial College London,
London, UK/manova Ltd,
Imperial College London,
London, UK
Olga Ciccarelli
Queen Square Multiple
Sclerosis Centre, Institute
of Neurology, University
College London, London, UK

Magnetic resonance spectroscopy (MRS) enables
measurement of a range of brain metabolites in vivo.
Two metabolites in relatively high concentration,
myo-inositol and N-acetyl aspartate (NAA), are
among those showing pathology-related changes in
MS.3 Myoinositol has been proposed as a glial

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